Theradigm has a goal to develop and deliver cell based therapy for neurological disease or injury. In recent years tremendous advances are made in the field of cell therapy to repair injured tissue. But the cell therapy field still faces the challenges of consistently expanding the therapeutic cells in large enough quantities without immortalizing them for their use in human clinical trials. We are proposing to manufacture human fetal brain and spinal cord derived neural stem cells (NSCs) under physiological oxygen levels (3%). Based on our preliminary data and other research reports we hypothesize that expansion of NSCs under lower than atmospheric oxygen (20%) will increase their expansion rate while maintaining their multipotency. We will first identify the most optimum growth conditions to expand these cells in vitro. We will then characterize these cells for their stem cell properties by looking for expression of stem cell specific markers by Flow cytometry and quantitative PCR. Their multipotential by differentiating them and measuring expression of brain lineage specific genes by quantitative PCR. We will define their phenotype by gene profile on microarrays and expression of cell surface markers by Flow cytometry. By high-resolution array- based copy number analysis, HLA typing, SIR typing and karyotyping we will determine genomic stability of NSCs grown under reduced oxygen. After defining their identity (molecular, phenotypic, immunologic, genotypic) we will use the optimum growth conditions to manufacture and bank these cells. These well characterized cells will be used in Phase II study to determine engraftment and efficacy of these cells in animal spinal cord injury models. These studies will help us with our long-term goal to develop cell therapy to improve morbidity and health care cost for patients suffering from spinal cord injury. If we can manufacture NSCs in large enough quantities, we can also test efficacy of them in other neurological disorders and injuries like stroke and traumatic brain injury. We will also be able to apply this cell manufacturing process to other cell types like bone marrow and adipose tissue derived stem cells. [unreadable] [unreadable] [unreadable]